Increased Serotonin and Dopamine Transporter Binding in Psychotropic Medication–Naïve Patients with Generalized Social Anxiety Disorder Shown by 123I-β-(4-Iodophenyl)-Tropane SPECT

There is circumstantial evidence for the involvement of serotonergic and dopaminergic systems in the pathophysiology of social anxiety disorder. In the present study, using SPECT imaging we examined the 123I-β-(4-iodophenyl)-tropane binding potential for the serotonin and dopamine transporters in patients with a generalized social anxiety disorder and in age- and sex-matched healthy controls. Methods: Twelve psychotropic medication–naïve patients with social anxiety disorder, generalized type (5 women and 7 men) and 12 sex- and age-matched healthy controls were studied. Volumes of interest were constructed on MRI-coregistered SPECT scans. Binding ratios were compared using the Mann–Whitney U test. Possible correlations between binding patterns and symptomatology were assessed using the Spearman rank correlation coefficient. Results: Significantly higher binding potentials were found for the serotonin in the left and right thalamus of patients. Patients had also a significantly higher binding potential for the dopamine transporter in the striatum. Conclusion: The present study provided direct evidence for abnormalities in both the dopaminergic and the serotonergic systems in patients with generalized social anxiety disorder.

[1]  J Tauscher,et al.  Imaging serotonin and dopamine transporters with 123I-beta-CIT SPECT: binding kinetics and effects of normal aging. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[2]  S. Kasper,et al.  [123I] β-CIT and single photon emission computed tomography reveal reduced brain serotonin transporter availability in bulimia nervosa , 2001, Biological Psychiatry.

[3]  M. Hamilton,et al.  Development of a rating scale for primary depressive illness. , 1967, The British journal of social and clinical psychology.

[4]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[5]  J J Bartko,et al.  ON THE METHODS AND THEORY OF RELIABILITY , 1976, The Journal of nervous and mental disease.

[6]  M. Nader,et al.  Effect of social status on striatal dopamine D2 receptor binding characteristics in cynomolgus monkeys assessed with positron emission tomography , 1998, Synapse.

[7]  J. Tiihonen,et al.  Dopamine reuptake site densities in patients with social phobia. , 1997, The American journal of psychiatry.

[8]  T. Hergueta,et al.  The mini international neuropsychiatric interview , 1998, European Psychiatry.

[9]  E. Hollander,et al.  Serotonergic function in social phobia: comparison to normal control and obsessive–compulsive disorder subjects , 1998, Psychiatry Research.

[10]  Wolfgang Wadsak,et al.  Reduced Serotonin-1A Receptor Binding in Social Anxiety Disorder , 2007, Biological Psychiatry.

[11]  Murray B. Stein,et al.  Striatal Function in Generalized Social Phobia: A Functional Magnetic Resonance Imaging Study , 2007, Biological Psychiatry.

[12]  H. Westenberg,et al.  Social anxiety disorder and generalized anxiety disorder: serotonergic and dopaminergic neurocircuitry. , 2002, The Journal of clinical psychiatry.

[13]  J. Davidson,et al.  Efficacy of olanzapine in social anxiety disorder: a pilot study , 2002, Journal of psychopharmacology.

[14]  Alexander Neumeister,et al.  [123I]-β-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder , 2000, Biological Psychiatry.

[15]  Alan A. Wilson,et al.  Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study. , 2001, The American journal of psychiatry.

[16]  R. Mailman,et al.  Neuroendocrine responsivity to monoaminergic system probes in generalized social phobia. , 1994, Anxiety.

[17]  Qian Li,et al.  Genetic perspectives on the serotonin transporter , 2001, Brain Research Bulletin.

[18]  P. Tibbo,et al.  Toward an integrative understanding of social phobia. , 2001, Journal of psychiatry & neuroscience : JPN.

[19]  Brian Knutson,et al.  Selective alteration of personality and social behavior by serotonergic intervention. , 1998, The American journal of psychiatry.

[20]  D. Stein,et al.  Consensus statement on generalized anxiety disorder from the International Consensus Group on Depression and Anxiety. , 2001, The Journal of clinical psychiatry.

[21]  Marc Laruelle,et al.  Central serotonin transporter availability measured with [123I]beta-CIT SPECT in relation to serotonin transporter genotype. , 2004, The American journal of psychiatry.

[22]  N. V. D. Van der Wee,et al.  Enhanced dopamine transporter density in psychotropic-naive patients with obsessive-compulsive disorder shown by [123I]{beta}-CIT SPECT. , 2004, The American journal of psychiatry.

[23]  H. Westenberg,et al.  Consensus statement on social anxiety disorder from the International Consensus Group on Depression and Anxiety. , 1998, The Journal of clinical psychiatry.

[24]  R. Ebstein,et al.  Relation of shyness in grade school children to the genotype for the long form of the serotonin transporter promoter region polymorphism. , 2003, The American journal of psychiatry.

[25]  M. Liebowitz,et al.  Psychometric properties of the Liebowitz Social Anxiety Scale , 1999, Psychological Medicine.

[26]  L. Reneman,et al.  Validation of [123I]β-CIT SPECT to Assess Serotonin Transporters In Vivo in Humans: a Double-Blind, Placebo-Controlled, Crossover Study with the Selective Serotonin Reuptake Inhibitor Citalopram , 2005, Neuropsychopharmacology.

[27]  Robert B. Innis,et al.  Graphical, Kinetic, and Equilibrium Analyses of in vivo [123I]β-CIT Binding to Dopamine Transporters in Healthy Human Subjects , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[28]  D. Collins,et al.  Automatic 3D Intersubject Registration of MR Volumetric Data in Standardized Talairach Space , 1994, Journal of computer assisted tomography.

[29]  P. Cowen,et al.  Tryptophan depletion decreases the recognition of fear in female volunteers , 2003, Psychopharmacology.

[30]  I. Heuser,et al.  Anxiety disorders in patients with Parkinson's disease. , 1990, The American journal of psychiatry.

[31]  R. Hu.  Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) , 2003 .

[32]  J. Ballenger,et al.  Plasma and CSF HVA levels in panic patients with comorbid social phobia , 1994, Biological Psychiatry.

[33]  J M Gorman,et al.  Neurobiological mechanisms of social anxiety disorder. , 2001, The American journal of psychiatry.

[34]  M. Liebowitz,et al.  Low dopamine D(2) receptor binding potential in social phobia. , 2000, The American journal of psychiatry.

[35]  D. Perrett,et al.  Acute SSRI Administration Affects the Processing of Social Cues in Healthy Volunteers , 2003, Neuropsychopharmacology.

[36]  R. C. Oldfield.  The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[37]  J. Karhu,et al.  Imaging of serotonin and dopamine transporters in the living human brain , 1995, European Journal of Nuclear Medicine.

[38]  I. Podreka,et al.  β-CIT SPECT demonstrates blockade of 5HT-uptake sites by citalopram in the human brain in vivo , 2005, Journal of Neural Transmission / General Section JNT.

[39]  J Tauscher,et al.  [123I]-beta-CIT SPECT imaging shows reduced brain serotonin transporter availability in drug-free depressed patients with seasonal affective disorder. , 2000, Biological psychiatry.

[40]  D. Nutt,et al.  Tryptophan depletion reverses the therapeutic effect of selective serotonin reuptake inhibitors in social anxiety disorder , 2004, Biological Psychiatry.

[41]  H. Westenberg.  The nature of social anxiety disorder. , 1998, The Journal of clinical psychiatry.